Genetic 'typos' open new doors in breast cancer research

VANCOUVER — The 32 genetic "typos" are tiny, but they tell an intriguing story of one women’s breast cancer.

Five gene mutations played lead roles when her cancer first showed up, with another six mutations in supporting roles. When tumours recurred nine years later, 19 new mutations, and a couple of new bit players, were helping the cancer grow and spread.

The findings, by a team at the B.C. Cancer Agency, give an unprecedented glimpse of how breast cancer evolves.

And it highlights the need to rethink the way cancer is treated from the get-go, says oncologist Dr. Samuel Aparicio, lead author of a report on the findings in the journal Nature on Thursday.

There were several different mutations creating different types of cancer cells in the women's tumour right from the beginning — underscoring the need for multi-pronged treatment, he says.

“The point is, unless we start thinking about targeting the cancer with multiple drugs at the beginning, we’re going to go on seeing treatment failures,” Aparicio told Canwest News.

The researchers do not know the identity or fate of the British Columbia women who donated samples of her cancer tissues to research. But the story of her mutations has landed on the cover of the noted research journal under the headline A Cancer Evolves.

Aparicio says its been known for years that breast cancer mutates and evolves as it grows and spreads. What sets the new work apart is that it provides “a really high resolution picture of that happening in a patient.”

To chart the changes, the researchers sequenced the long chains of DNA, comprised of billions of biochemical building blocks, inside cells from her original cancer. They then sequenced the DNA from cells in the breast cancer that reappeared nine years later.

After combing through the genomes, the researches were able to pinpoint 32 key mutations — or biochemical “typos” — driving the cancer. While the scientists could clearly see 19 new mutations when the cancer returned, they don't know if they were created by the radiation therapy the women received, or natural evolution of the cancer.

Aparicio says it took 18 months and cost “tens of thousands” of dollars to pinpoint the mutations. Now that they have worked out the technique, he says they are sequencing several cancers a week as part of the search for mutations in different types of breast cancer.

Aparicio, who holds a Canada research chair in molecular oncology, says more personalized treatment that sequences each patient’s cancer could soon be within reach given the dropping costs and “phenomenal” increase in the power and speed of gene sequencing.

“Within a few years, we might be able to get the cost down to a few thousand dollars per patient,” he says. That's no more expensive than some cancer diagnostic tests used today.

Having a detailed map of each patient’s mutations would, at least in theory, allow doctors to better target and tailor cancer therapies, which can be prohibitively expensive.

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